title: Proliferative phenotype of pulmonary microvascular endothelial cells plays a critical role in the overexpression of CTGF in the bleomycin-injured rat.
abstract: The pathogenesis of idiopathic pulmonary fibrosis (IPF) is not very clear, with evidence for the involvement of both inflammation and aberrant vascular remodeling (associated with angiogenesis). Pulmonary microvascular endothelial cells (PMVECs), which play a major role in inflammation, secrete cytokines that promote the transformation and collagen synthesis of fibroblasts. Moreover, angiogenesis is characterized by PMVEC proliferation. The main aim of this study was to confirm the role of PMVECs in pulmonary fibrosis. Accordingly, we observed the functional changes in PMVECs in bleomycin (BLM)-treated rats (pulmonary fibrosis model) in vivo, and compared them with those of rats with pneumonia. The proliferation phenotype and intracellular ionized calcium concentration ([Ca(2+)]i) of PMVECs from BLM-treated rats were also investigated. The functioning of PMVECs was abnormal in BLM-injured rats, particularly with regard to their proliferation and secretion of connective tissue growth factor (CTGF). [Ca(2+)]i was increased in the proliferated PMVECs from BLM-treated rats. The findings suggest that dysfunction of PMVECs characterized by overexpression of CTGF is critical in rat pulmonary injury induced by BLM, and is probably related with the proliferative phenotype and [Ca(2+)]i overload. It can be concluded from the results that proliferation of PMVECs plays an important role in the pathogenesis of BLM-induced PF.
authors.affiliation: Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, PR China.
authors.forename: Lin-Feng
authors.initials: LF
authors.lastname: Yan
authors.forename: Ya-Ning
authors.initials: YN
authors.lastname: Wei
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Nan
authors.forename: Qian
authors.initials: Q
authors.lastname: Yin
authors.forename: Yue
authors.initials: Y
authors.lastname: Qin
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Bao-Ying
authors.initials: BY
authors.lastname: Chen
authors.forename: Ge
authors.initials: G
authors.lastname: Zhao
authors.forename: Jing-Guo
authors.initials: JG
authors.lastname: Wei
authors.forename: Guang-Bin
authors.initials: GB
authors.lastname: Cui
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001761:Bleomycin / Q000633:toxicity; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology*; D008168:Lung / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D000903:Antibiotics, Antineoplastic; C526316:CCN2 protein, rat; D001761:Bleomycin; D055513:Connective Tissue Growth Factor; D002118:Calcium
keywords: Aberrant vascular remodeling; Bleomycin; Inflammation; Proliferative endothelial cells; Pulmonary fibrosis